MOLECULE

Farnesol

Farnesol belongs to the class of organic compounds known as sesquiterpenoids. These are terpenes with three consecutive (5-carbon) isoprene units. Thus, farnesol is considered to be an isoprenoid lipid molecule. Farnesol pyrophosphate (formed by the reaction of geranyl pyrophosphate reacts with isopentenyl pyrophosphate) is the building block of all acyclic sesquiterpenes. Two sesquiterpenes are paired to form squalene (a 30-carbon terpenoid), which is the precursor for all steroids in plants, animals, and fungi. Farnesol is a very hydrophobic molecule, practically insoluble in water but miscible with oil. Under standard conditions, it is a colorless liquid. Farnesol is present in many essential oils such as citronella, neroli, cyclamen, lemon grass, tuberose, rose, musk, balsam and tolu. It is widely used in perfumery to emphasize the odors of sweet floral perfumes. In addition to being a perfuming agent, farnesol is a natural pesticide for mites and is a pheromone for several other insects. It also exhibits anti-microbial activity. In fact, farnesol is used as a deodorant in cosmetic products because of its anti-bacterial activity (PMID: 18492144). Farnesol has also been shown to function as a chemopreventative and anti-tumor agent through the inhibition of phosphatidylcholine biosynthesis, the induction of apoptosis, inhibition of cell cycle progression and actin cytoskeletal disorganization (PMID: 19520495). These actions appear to be mediated through farnesol’s regulation/inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and CTP:phosphocholine cytidylyltransferase alpha (CCTalpha). HMG-CoA is the rate-limiting enzyme in the mevalonate pathway and CCTalpha is the rate limiting enzyme in phosphatidylcholine biosynthesis (PMID: 19520495). Farnesol has also been shown to activate the farnesoid receptor (FXR), a nuclear receptor that forms a functional heterodimer with RXR (Retinoic X receptor). The physiological ligand for FXR remains to be identified; farnesol, may simply mimic the unidentified natural ligand(s). A possible metabolic fate for farnesol is its conversion to farnesoic acid, and then to farnesol-derived dicarboxylic acids (FDDCAs), which would then be excreted in the urine. Farnesol can also be oxidized to a prenyl aldehyde, presumably by mitochondrial or peroxisomal alcohol dehydrogenases (ADH). Liver endoplasmic reticulum and peroxisomal fractions are able to phosphorylate farnesol to farnesyl diphosphate in a cytosine triphosphate (CTP) dependent fashion. (PMID: 9812197, 8636420, 9083051, 9015362).